P1391: VARNIMCABTAGENE AUTOLEUCEL (VAR-CEL) IN RELAPSED/ REFRACTORY CD19+ NON-HODGKIN LYMPHOMA
Authors: Nuria Martinez-Cibrian, Valentín Ortiz-Maldonado, Marta Español-Rego, Daniel Benitez-Ribas, Joan Cid, Miquel Lozano, Sergio Navarro, Laura Magnano, Eva Gine, Juan Gonzalo Correa Saldarriaga, Pablo Mozas, Luis Gerardo Rodríguez Lobato, Helena Brillembourg, Mercedes Montoro, Pilar Ayora, Leticia Alserawan, Alexandra Martínez Roca, Armando Lopez-Guillermo, Avaro Urbano Ispizua, Manel Juan, Mariona Pascal, Julio Delgado
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Varnimcabtagene autoleucel (var-cel, ARI-0001 cells), an academic second generation anti-CD19 CAR T-cell, has been granted hospital exemption use by the AEMPS and PRIME designation by the EMA for patients >25 years old with relapsed or refractory (R/R) B cell acute lymphoblastic leukaemia (B-ALL) based on the results of the CART19-BE-01 clinical trial (NCT03144583). Currently, var-cel is also being used as a compassionate use (CU) for adult patients with R/R CD19+ non-Hodgkin lymphoma (NHL). Aims: Here we report outcomes from all consecutive patients with R/R CD19+ NHL referred for treatment with var-cel either within the clinical trial or in the CU program. Methods: Fifty-one consecutive patients signed the consent form at our institution from July/17 to September/22. Ten patients were enrolled in the original trial and the subsequent 41 in the CU program. Patients underwent lymphodepletion with fludarabine (30mg/m2) and cyclophosphamide (300mg/m2). Target dose was 1-5 x106 CAR T cells/kg which was split in 3 fractions (10%, 30% and 60%). Results: Apheresis was performed in all 51 patients, 45 patients received at least one dose of var-cel: 45% were female; median age was 55 years (range 19-74); median prior lines was 4 (range 2-9); and 35% had a prior autologous stem cell transplant. Median follow-up was 12.8 months (range 3.9-44.6). Specific histologic subtypes are displayed in Table 1. Median vein-to-vein time was 29 days (range 18-182) and median time from screening to infusion was 40 days (range 23-195). Forty-one patients (80%) received bridging therapy. CRS rate was 84%, only 2 cases (4%) had grade ≥3 CRS. ICANS occurred in 3 patients (7%), one patient (2%) had grade ≥3 ICANS. 43 patients (96%) had grade ≥3 neutropenia and 24 (56%) grade ≥3 thrombocytopenia, but only one patient required a CD34+ boost for persistent cytopenia. One patient died due to severe sepsis and toxic epidermal necrolysis. The pre-specified overall response rate (ORR) (at day +100) was 73% (95% CI: 58-85%), with a complete response rate (CRR) of 64% (49-78%). Median duration of response (DOR) from response assessment (day +100) had not been reached, and was 56% (39-81%) at 3 years. Median progression-free survival (PFS) was 10.4 months (6.48-NE) and median overall survival (OS) had not been reached. At 3 years, estimated PFS and OS were 40% (26-61%) and 52% (36-76%), respectively. Median duration of absolute B-cell aplasia (BCA) had not been reached and was estimated as 69% (52-91%) at 3 years. The cumulative incidence of relapse/progression was 53% at 3 years (37-71%). Table 1 shows efficacy results by histological subtype. Univariate analysis revealed that both histology (indolent vs. aggressive) and serum LDH (normal vs. abnormal) had a significant impact on PFS. However, in multivariate analysis only LDH retained its prognostic impact. Patients with increased LDH had a shorter median PFS compared to those with normal LDH (6.1 months vs not reached, p = 0.006). Summary/Conclusion: High percentage of included patients received var-cel treatment. Var-cel had an acceptable safety profile in adult patients with R/R CD19+ NHL. Efficacy results may be comparable to other commercial CD19 CAR T cell products. Long-term persistent absolute BCA was achieved in the majority of patients. In multivariate analysis, only abnormal LDH had a significant impact on PFS.Keywords: CAR-T, Cellular therapy, NHL